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Browsing by Author "Herbert, Nicholas Graeme."

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    Investigating the impact of HIV infection on ILC3s in human lymph nodes.
    (2022) Herbert, Nicholas Graeme.; Kloverpris, Henrik.
    People living with HIV (PLWH) develop extensive fibrosis and collagen deposition throughout their lymphoid tissues not reversed by antiretroviral therapy (ART). Innate lymphoid cells (ILCs) play essential roles in tissue homeostasis and repair, however, no studies exist on ILCs in lymph nodes (LNs) during HIV infection. We hypothesized that ILCs are modulated by HIV infection and are involved in the subsequent immune responses. We obtained fresh celiac, cystic, bile, falciform, common hepatic and mesenteric LNs immediately after gastrointestinal surgery from patients recruited from areas in KwaZulu-Natal, South Africa – home to the highest HIV prevalence in the world. LNs from PLWH receiving ART exhibited extensive collagen deposition compared to uninfected controls characteristic of HIV-infected LN pathology. Single-cell transcriptional profiling revealed activation of the dominant ILC3 subset during HIV infection, suggesting ILC3s are directly involved in the HIV immune response. HIV-infected LNs expressed more heterogenous ILC3 subsets, including ‘ex-ILC3s’. We found signatures suggesting that HIV infection induces terminal differentiation of homeostatic ILC3 populations, whereby an ex-ILC3 population becomes distinct and may contribute to a type 1 immune response. Since HIV infection leads to sustained inflammation in LNs, this terminal differentiation and emergence of ex-ILC3s may be irreversible. Moreover, we found elevated levels of TGF production by ILC3s during HIV infection which may suggest that these cells play a role in fibrosis formation, directly or indirectly, through fibroblast-induced collagen deposition. Here, I performed the first singlecell analysis of ILCs in HIV-infected LNs and identified ILC3s as potential contributors to LN fibrosis, a major pathological consequence of HIV infection that warrants further investigation